Muta Tatsushi
Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Vitam Horm. 2006;74:301-16. doi: 10.1016/S0083-6729(06)74012-2.
The innate immune system responds to various microbial substances to elicit production of cytokines, chemokines, and costimulatory molecules that regulate activation of the acquired immune system. Although the transcription factor nuclear factor (NF)-kappaB plays central roles in the induction, it remains to be clarified how appropriate genes are selectively activated with appropriate timing and duration by the multifunctional transcription factor after integration of signals activated by invasion of various pathogens. IkappaB-zeta is barely detectable in resting cells and is strongly induced upon stimulation of the innate immune system. The induced IkappaB-zeta associates with the NF-kappaB subunit in the nucleus and regulates its transcriptional activity both positively and negatively depending on genes. Thus, the innate immune system utilizes NF-kappaB as a major transcription factor and modulates its activity in a gene-specific manner by the regulatory factor IkappaB-zeta, which is specifically induced upon stimulation of the innate immune system. This multistep regulation of the transcription would be fundamental in selective expression of genes upon cell activation.
固有免疫系统对各种微生物物质作出反应，引发细胞因子、趋化因子和共刺激分子的产生，这些分子可调节获得性免疫系统的激活。尽管转录因子核因子（NF）-κB在诱导过程中起核心作用，但在整合由各种病原体入侵激活的信号后，多功能转录因子如何在适当的时间和持续时间内选择性地激活合适的基因仍有待阐明。IκB-ζ在静息细胞中几乎检测不到，在固有免疫系统受到刺激时会被强烈诱导。诱导产生的IκB-ζ在细胞核中与NF-κB亚基结合，并根据基因的不同对其转录活性产生正向和负向调节。因此，固有免疫系统利用NF-κB作为主要转录因子，并通过在固有免疫系统受到刺激时特异性诱导产生的调节因子IκB-ζ以基因特异性方式调节其活性。这种转录的多步骤调节对于细胞激活时基因的选择性表达至关重要。
